Plasticity in the nervous system is suggested whenever animals show improvements in their capacity to behave appropriately. Such is the case following learning or development. In this project we focus on another example of plasticity, recovery of function following specific damage to the dopamine-containing neurons in the brain. We intend to address this issue at the cellular level, using biochemical procedures to determine whether adaptive changes occur in residual elements of the damaged system. In particular, we will determine the capacity of neurons to synthesize and release dopamine, we will measure the number and sensitivity of receptors within target tissue in corpus striatum, and we will determine the functional state of these receptors by measuring dopamine-mediated cAMP production and acetylcholine turnover. A more integrated picture of these events will be provided by in vivo voltammetry, which will permit us to study the possible diffusion of dopamine from the intact terminals to the denervated tissue, and by electrophysiological recording from these target neurons in the striatum, both under basal conditions and after electrical stimulation of the residual dopaminergic neurons. We also will address the same issue in a different model by studying adrenal medullary function after destruction of the sympathetic nerves, in which catecholamine synthesis and release can be more easily manipulated and monitored. We believe that our results will have significance for questions of neurnal plasticity as well as direct relevance to several clinical issues in which brain dopamine-containing neurons have been implicated, including Parkinson's disease, schizophrenia, and affective disorders.